Fri Apr 22 2022

84 articles - From Saturday Apr 16 2022 to Friday Apr 22 2022

parm_toc.knit

Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…


Meta-analysis

meta-analyses and systematic reviews

Thromb Haemost

Safety and efficacy of selective, clopidogrel-based strategies in acute coronary syndrome: a study-level meta-analysis.

As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.

Pubmed   Journal   ReadQx 


Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

Immunoglobulin Light Chain Amyloidosis: 2022 Update on Diagnosis, Prognosis, and Treatment.

In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax and bendamustine. Future challenges Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.

Pubmed   Journal   ReadQx 

Ann Oncol

Cancer risk in individuals with autism spectrum disorder.

ASD per se is not associated with an increased risk for cancer in early life. The increased cancer risk among individuals with ASD is likely mainly attributable to co-occurring intellectual disability and/or birth defects in ASD.

Pubmed   Journal   ReadQx 

Blood

A TCR Mimic CAR T Cell Specific for NDC80 Is Broadly Reactive With Solid Tumors and Hematological Malignancies.

CAR T cells directed against the ALNEQIARL:HLA-A*02 complex demonstrated high sensitivity and specificity for recognition and killing of multiple cancer types, especially those of hematological origin and were efficacious in mouse models against a human leukemia and a solid tumor. In contrast, no toxicities towards resting or activated healthy leukocytes as well as hematopoietic stem cells were observed. This demonstrates how MS can inform the design of broadly reactive therapeutic TCR mimic CAR T cell therapies that can target multiple cancer types currently not druggable by small molecules, conventional CAR T cells, T cells or antibodies.

Pubmed   Journal   ReadQx 

Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia.

This leads to transcription of the BH3-only protein, Noxa, and degradation of the pro-survival Mcl-1 protein on which AML cells are highly dependent on for survival. Targeting this novel ISR pathway in combination with the Bcl-2 inhibitor venetoclax synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anti-cancer effects of ceramide and pre-clinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.

Pubmed   Journal   ReadQx 

Cryo-EM structure of the prothrombin-prothrombinase complex.

The 696YDYQNRL702 segment binds to prothrombin and establishes the pathway of activation by sequestering R271 against D697 and directing R320 toward the active site of fXa. The structure provides a molecular view of prothrombin activation along the meizothrombin pathway and suggests a mechanism for cleavage at the alternative R271 site. The findings advance our basic knowledge of a key step of the coagulation response and bear broad relevance to other macromolecular interactions in the blood.

Pubmed   Journal   ReadQx 

Determinants of splenectomy long-term outcomes in pediatric autoimmune cytopenias.

Diagnosis of an IM at any timepoint during follow-up was associated with an even lower FFS (HR 0.22, 95% CI 0.12-0.39, p = 2.8x10-7, adjusted for AIC subtype) as well as with higher risk of recurrent or severe bacterial infections and thrombosis. In conclusion, our results support the search for associated IMs when considering a splenectomy to refine the risk-benefit ratio. After the procedure, monitoring IMs helps to identify patients with higher risk of unfavorable outcome.

Pubmed   Journal   ReadQx 

Disruption of dNTPs Homeostasis by Ribonucleotide Reductase Hyperactivation Overcomes AML Differentiation Blockade.

Mechanistically, excessive activation of ERK signaling downstream of the imbalance contributes to cellular outcomes of RNR hyperactivation. A CRISPR screen identifies a synthetic lethal interaction between loss of DUSP6, an ERK negative regulator, and nelarabine treatment. These data demonstrate that dNTP homeostasis governs leukemia maintenance, and combination of DUSP inhibition and nelarabine represents a therapeutic strategy.

Pubmed   Journal   ReadQx 

Donor Plasmacytoid Dendritic Cells Limit Graft-versus-Host Disease Through Vasoactive Intestinal Polypeptide Expression.

BMT recipients of VIP-KO pDCs had more Th1 polarized T cells, and higher plasma levels of GM-CSF and TNF-alpha than recipients of wild-type pDCs. T cells from VIP-KO pDC recipients had increasing levels of bhlhe40 transcripts during the first two weeks post-transplant, and higher levels of CyclophilinA/Ppia transcripts at day 15 compared with T cells from recipients of wild type pDCs. Collectively, these data indicate paracrine VIP synthesis by donor pDCs limits pathogenic T cell inflammation, supporting a novel mechanism by which donor immune cells regulate T cell activation and GvHD in allogeneic BMT.

Pubmed   Journal   ReadQx 

Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL.

Although sensitivity analyses using either PET or CT-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel versus axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.

Pubmed   Journal   ReadQx 

Long-term Outcomes for Ibrutinib-Rituximab and Chemoimmunotherapy in CLL: Updated Results of the E1912 Trial.

In conclusion, Ibrutinib-rituximab therapy offers superior PFS relative to FCR in both IGHV mutated and unmutated CLL patients as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. Clinical trial at NCT02048813.

Pubmed   Journal   ReadQx 

Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis.

This leads to increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of SRC, PYK2 and myosin light chain resulting in opening of the endothelial barrier. Mice with endothelium-specific Piezo1 deficiency show decreased leukocyte extravasation in different inflammation models. Thus, leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis.

Pubmed   Journal   ReadQx 

Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study.

DDX41MutGL patients displayed higher complete remission (CR) rates (94% vs 69%, p<0.0001) and longer restricted mean overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) than ELN-2017 intermediate/adverse (Int/Adv) DDX41WT patients (5-year RMST of 13.6 months, p < 0.001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to join that of Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first CR was associated with prolonged relapse-free survival (RFS; HR, 0.43 [95%CI, 0.21-0.88]; p = 0.02) but not with longer OS (HR=0.77 [95%CI, 0.35-1.68], p=0.5).

Pubmed   Journal   ReadQx 

Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results.

The safety profile of rVWF was consistent with the previously established profile, with no new adverse drug reactions identified. Findings suggest that rVWF prophylaxis can reduce treated spontaneous BEs in patients previously receiving on-demand VWF therapy and maintains at least the same level of hemostatic control in patients who switch from prophylaxis with pdVWF to rVWF, with a favorable safety profile. : (#NCT02973087) and (#EudraCT 2016-001478-14).

Pubmed   Journal   ReadQx 

Resistance to mogamulizumab is associated with loss of CCR4 in Cutaneous T-cell Lymphoma.

We also report on outcomes of three cutaneous T-cell lymphoma patients with gain-of-function CCR4 mutations treated with mogamulizumab. Our study indicates that resistance to mogamulizumab in CTCL frequently involves loss of CCR4 expression and emergence of CCR4 genomic alterations. This finding has implications for management and monitoring of CTCL patients on mogamulizumab and development of future CCR4-directed therapies.

Pubmed   Journal   ReadQx 

The ERK2 DBP domain opposes pathogenesis of a JAK2V617F-driven myeloproliferative neoplasm.

Because inactivation of the ERK2-DBP created a functional ERK2 kinase limited to binding substrates through its D-domain, these data suggested that the D-domain substrates were responsible for promoting oncogene-induced progenitor growth and tumor progression, and that pharmacologic targeting of the ERK2-D domain might attenuate cancer cell growth. Indeed, pharmacologic agents targeting the ERK2-D domain were effective in attenuating the growth of JAK2-dependent myeloproliferative neoplasm cell lines. Taken together, these data indicate that the ERK-D and -DBP domains can play distinct roles in the progression of neoplasms and that the D-domain has the potential to be potent therapeutic target in Ras/MAPK dependent cancers.

Pubmed   Journal   ReadQx 

Blood Adv

A predictive model for bone marrow disease in cytopenia based on noninvasive procedures.

In a multivariable logistic regression, mutations in TET2, SF3B1, U2AF1, TP53 and RUNX1 were significantly associated with abnormal bone marrow morphology. In the validation cohort, a model combining mutational status and clinical data identified 34 patients (20%) without abnormal bone marrow morphology with a sensitivity of 100% (95%-CI: 93%-100%). Overall, we show that NGS combined with clinical data can predict the presence of abnormal bone marrow morphology in patients with unexplained cytopenia and thus can be used to assess the need of a bone marrow biopsy.

Pubmed   Journal   ReadQx 

Assessment of Systemic and Gastrointestinal Tissue Damage Biomarkers for GVHD Risk Stratification.

The algorithm that included only biomarkers of systemic inflammation (TNFR1+TIM3) had a significantly smaller area under the curve (AUC, 0.57) than the AUCs of algorithms that contained at least 1 GI damage biomarker (TNFR1+ST2, 0.70; TNFR1+REG3a, 0.73; ST2+REG3a, 0.79; al p<0.001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for al endpoints.

Pubmed   Journal   ReadQx 

ATG4A regulates human erythroid maturation and mitochondrial clearance.

Depletion of ATG4A in primary human hematopoietic stem and progenitor cells selectively impaired erythroid but not myeloid lineage differentiation, resulting in reduced red cell production, delayed terminal differentiation, and impaired enucleation. Loss of ATG4A impaired autophagy and mitochondrial clearance, giving rise to reticulocytes with retained mitochondria and autophagic vesicles. In summary, our study identifies ATG4A as a cell type-specific regulator of autophagy in erythroid development.

Pubmed   Journal   ReadQx 

Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma.

There were no differences in PFS in unadjusted (HR 0.87 [95% CI 0.53-1.41], p=0.56) or adjusted (HR 0.79 [95% CI 0.45-1.37], p=0.40) comparisons. There were no clear differences in secondary endpoints in unadjusted or adjusted analyses. This retrospective adjusted comparison of two independent cohorts of younger patients with MCL suggests that R-B with ASCT and maintenance rituximab is a feasible and effective first-line treatment, with outcomes comparable to R-CHOP/R-DHAP with ASCT.

Pubmed   Journal   ReadQx 

Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern.

We observed a 2- to 4-fold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to delta or omicron, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-delta COVID-19/post-vaccination units and the hyperimmunoglobulin effectively neutralized al three variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

Pubmed   Journal   ReadQx 

Defenestrated endothelium delays liver-directed gene transfer in hemophilia A mice.

Surprisingly, compared to control mice, FVIII knockout (F8TKO) mice showed significant delay in AAV8-GFP transfer in the liver. We found that the delay in liver directed gene transfer in F8TKO mice was associated with absence of liver sinusoidal endothelial cell (LSEC) fenestration, which led to aberrant expression of several sinusoidal endothelial proteins causing increased capillarization and decreased permeability of LSECs. This is the first study to link impaired liver-directed gene transfer to liver-endothelium maladaptive structural changes associated with FVIII deficiency in mice.

Pubmed   Journal   ReadQx 

Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease.

For instance, in six type 1 patients with exon 4-5 deletion, mean VWF activity at 1 hour after desmopressin was 0.81 IU/mL with a coefficient of variation of 22.9%. In conclusion, al type 1 VWD patients without a VWF gene variant respond to desmopressin. In type 1 and type 2 VWD patients with a VWF variant, desmopressin response highly depends on the VWF gene variants.

Pubmed   Journal   ReadQx 

Efficacy of combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia.

The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. #NCT03413306.

Pubmed   Journal   ReadQx 

Favorable Outcomes Following Allogeneic Transplantation in Adults with Hemophagocytic Lymphohistiocytosis.

Infectious complications and GVHD outcomes were comparable to standard RIC transplantation at our institute. Mixed chimerism was common but did not correlate with transplant outcomes. Our data suggests that the immune defect in HLH can be abrogated with allogeneic transplantation using a reduced intensity regimen with early administration of alemtuzumab as pre-conditioning, providing a potentially curative option for this difficult disease.

Pubmed   Journal   ReadQx 

HLA-DR expression on monocytes and outcome of anti-CD19 CAR-T cell therapy for large B-cell lymphoma.

For toxicity management, tocilizumab was more frequently used in the low mHLA-DR D-7 group. These data suggest that monocyte dysregulation prior to LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment, and is associated with failure of anti-CD19 CAR-T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field to improve CAR therapy.

Pubmed   Journal   ReadQx 

HSCT using carrier donors for CD40L deficiency results in excellent immune function and higher CD40L expression in cTfh.

All patients engrafted, achieved excellent immune reconstitution with lack of opportunistic infections, GVHD, immune dysregulation and stable CD40L expression mimicking that of donors 1-5 years post-HSCT. Immunoglobulin independence was achieved in three of the four patients. We demonstrate higher CD40L expression in carriers' cTfh compartment and excellent immune reconstitution using carrier donors in CD40L deficiency patients.

Pubmed   Journal   ReadQx 

MicroRNA serum profiles and chronic graft versus host disease.

Furthermore, five distinct miRNAs; miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and validated by receiver operating characteristics (ROC) analysis. Based on only three miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature which by bioinformatic approaches and linear regression model utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings.

Pubmed   Journal   ReadQx 

Platelet activation by SARS-CoV-2 implicates the release of active tissue factor by infected cells.

Increased TF mRNA expression and activity were also found in lungs in a murine model of COVID-19 and in plasma of severe COVID-19 patients, respectively. In summary, TF activity from SARS-CoV-2-infected cells activates thrombin, which signals to PARs on platelets. Blockade of molecules in this pathway may interfere in platelet activation and coagulation that is characteristic of COVID-19.

Pubmed   Journal   ReadQx 

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL.

Postinfusion, CD8+ CAR T cells had a proliferative advantage over CD4+ CAR T cells, and at peak expansion had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation had sustained, durable responses. In summary, initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy, while highlighting the impact of pre-infusion disease burden on outcomes.

Pubmed   Journal   ReadQx 

Respiratory viruses in hematopoietic cell transplant candidates: impact of preexisting lower tract disease on outcomes.

Thus, the presence of LRD due to common respiratory viruses, including HRV, before myeloablative allogeneic HCT was associated with increased mortality and hospitalization. Pretransplant URI due to HRV and endemic HCoV was not associated with these outcomes. Improved management strategies for pretransplant LRD are warranted.

Pubmed   Journal   ReadQx 

Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial is registered at as NCT02627053.

Pubmed   Journal   ReadQx 

Transcutaneous ultrasound mediated gene delivery into canine livers achieves therapeutic levels of FVIII expression.

Plasmid copy numbers correlated with hFVIII antigen levels and plasmid-derived mRNA was detected in treated livers. Liver transaminase levels and histology analysis indicated minimal liver damage and a rapid recovery post-treatment. These results indicate that liver-targeted transcutaneous UMGD is promising as a clinically feasible therapy for hemophilia A and other diseases.

Pubmed   Journal   ReadQx 

Blood Cancer J

A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma.

Variables associated with increased risk of severe infection in the first 4months included serum albumin =30g/L, ECOG>1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4months: low-risk (score 0-2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.

Pubmed   Journal   ReadQx 

Body mass index associated with monoclonal gammopathy of undetermined significance (MGUS) progression in Olmsted County, Minnesota.

Follow-up time was calculated from the date of MGUS to last follow-up, death, or progression to MM/another plasma-cell/lymphoid disorder. BMI (kg/m 2 . This association may be stronger among females.

Pubmed   Journal   ReadQx 

Exploring racial disparities in treatment patterns and outcomes for patients with multiple myeloma using real world data.

Adjusted rwOS estimates (for sex, age at index date, and practice type) to either first- (aHR=0.94; 95% CI: 0.84-1.06) or second-LOT (aHR=0.90; 95% CI: 0.77-1.05) were similar. Unadjusted derived response rate (dRR) during first-LOT was 84.8% (95% CI: 80.7-88.1) for Blacks and 86.9% (95% CI: 85.0-88.5) for Whites (odds ratio [OR]=0.78 [95% CI: 0.57-1.10]); in second-LOT, 67.2% (95% CI: 58.4-75.0) for Blacks and 72.4% (95% CI: 68.1-76.3) for Whites (OR=0.72 [95% CI: 0.46-1.13]). High representation of Black patients enabled this robust analysis, albeit with limitations inherent to the observational data source, the retrospective design, and the analytic use of newly derived endpoints requiring further validation.

Pubmed   Journal   ReadQx 

Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects.

Using chemical proteomics and biophysical methods, we identified the hydrophobic pocket of phosphodiester 6 subunit delta (PDE6D), a known RAS chaperone, as a target for this compound. Inhibition of RAS localization to the plasma membrane upon DW0254 treatment is associated with RAC inhibition through a phosphatidylinositol-3-kinase/AKT-dependent mechanism. Our findings provide new insights into the importance of PDE6D-mediated transport for RAS-dependent RAC activation and leukemic cell survival.

Pubmed   Journal   ReadQx 

Venetoclax combinations delay the time to deterioration of HRQoL in unfit patients with acute myeloid leukemia.

Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of =10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN+AZA vs PBO+AZA patients had longer TTD in GHS/QoL (P=0.066) and fatigue (P=0.189), and significantly longer TTD in PF (P=0.028) and HS-VAS (P MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.

Pubmed   Journal   ReadQx 

Haematologica

A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib.

Adjusted Cox proportional hazards model results showed that the del(17p)-present group was at significantly higher risk of death than the del(17p)-absent group (HR 1.70, P=0.0031). Event rates for switching to new treatment and discontinuation were higher but not statistically significant. The most common reason for ibrutinib discontinuation in both groups was toxicity, but discontinuation due to progression was significantly higher among del(17p)-present patients (20% vs 6%; P.

Pubmed   Journal   ReadQx 

A novel BCMA CAR-T-cell therapy with optimized human scFv for treatment of relapsed/refractory multiple myeloma: results from phase I clinical trials.

Not available.

Pubmed   Journal   ReadQx 

COVID-19 Infection in acute lymphoblastic leukemia over 15 months of the pandemic. A CAMPUS ALL report.

Not available.

Pubmed   Journal   ReadQx 

Crosstalk between ß-catenin and WT1 signalling activity in acute myeloid leukemia.

Not available.

Pubmed   Journal   ReadQx 

Evidence of protective effects of recombinant ADAMTS13* in humanized model for sickle cell disease.

rADAMTS13 also diminished H/R induced worsening of inflammatory vasculopathy, reducing local nitric oxidase synthase expression. Collectively, our data provide for the first-time evidence that pharmacologic treatment with rADAMTS13 (TAK-755) diminished H/R induced sickle cell related organ damage. Thus, rADAMTS13 might be considered as a potential effective disease-modifying treatment option for sickle cell related acute events.

Pubmed   Journal   ReadQx 

Hemostatic and protein C pathway dysfunction in the pathogenesis of experimental cerebral malaria.

Not available.

Pubmed   Journal   ReadQx 

Hereditary anemia caused by multilocus inheritance of PIEZO1, SLC4A1 and ABCB6 mutations: a diagnostic and therapeutic challenge.

Not available.

Pubmed   Journal   ReadQx 

Molecular assessment and the current limits of post-transplant prognostication for chronic myelomonocytic leukemia.

Not available.

Pubmed   Journal   ReadQx 

Persistent DNA damage and oncogenic stress-induced Trem1 promotes leukemia in mice.

Further analysis revealed that Trem1 expression in pre-leukemic HSCs and LSCs was associated with persistent DNA damage, prolonged oncogenic stress, and a strong inflammatory signature. Targeting several top Trem1 inflammatory signatures inhibits the proliferation of pre-leukemic HSCs and LSCs. Collectively, our observations uncover previously unknown expression and function of TREM1 in malignant stem cells, and identify TREM1 as a driver of leukemogenesis.

Pubmed   Journal   ReadQx 

The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis.

Nonetheless, the impact specifically of TP53 mutations should be interpreted cautiously given its rarity in CMML. We calculated the goodness of fit measured by Harrell's C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have provided the mutational landscape in patients with CMML who underwent alloHCT, and we demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond the CPSS.

Pubmed   Journal   ReadQx 

WT1 ß'ing catenin into shape: a new interaction driving epigenetic plasticity in AML?

Not available.

Pubmed   Journal   ReadQx 

Leukemia

CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+CS1 expressing CAR-T cells.

Since fratricide of CD8+cells occurred during production, we generated fratricide resistant CS1 deficient Luc90- CS1- CAR-T (CS1-Luc90- CS1- CAR-T). This led to protection of CD8+cells in the CAR-T cultures, but had no impact on efficacy. Our data demonstrate targeting the distal V domain of CS1 could be an effective CAR-T treatment for myeloma patients and deletion of CS1 in clinical production did not provide an added benefit using in vivo immunodeficient NSG preclinical models.

Pubmed   Journal   ReadQx 

GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity.

However, the interaction between GM-CSF and its upregulated receptors on CART cells was not the predominant mechanism of this activation phenotype. GM-CSF KO CART19 cell had reduced BH3 interacting-domain death agonist (Bid), suggesting an interaction between GM-CSF and intrinsic apoptosis pathways. In conclusion, our study demonstrates that CRISPR/Cas9-mediated GM-CSF knockout in CART cells directly ameliorates CART cell early activation and enhances anti-tumor activity in preclinical models.

Pubmed   Journal   ReadQx 

Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia.

No grade 3/4 infections were observed. Tisagenlecleucel expansion and long-term persistence were consistent with previous reports. Comparable to ALL patients without DS, tisagenlecleucel produced high remission rates, manageable side-effects, and promising long-term outcomes in pediatric/young adult patients with DS-ALL.

Pubmed   Journal   ReadQx 

Utility of the Treatment-Related Mortality (TRM) score to predict outcomes of adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation.

Consequently, relapse-free survival (RFS) and overall survival (OS) estimates progressively decreased (RFS at 3 years: 66% [59-72%] in Q1 vs 36% [29-42%] in Q4; OS at 3 years: 72% [66-78%] in Q1 vs 39% [33-46%] in Q4). With a C-statistic of 0.661 (continuous variable) or 0.642 (categorized by quartile), the TRM score predicted NRM better than the Pretransplantation Assessment of Mortality (PAM) score (0.603) or the HCT-CI/age composite score (0.576). While post-HCT outcome prediction remains challenging, these findings suggest that the TRM score may be useful for risk stratification for adults with AML undergoing allogeneic HCT.

Pubmed   Journal   ReadQx 

Thromb Haemost

CHIP and atherothrombotic risk.

Why this occurs is under rigorous investigation, but the majority of the studies to date suggest increased atherosclerosis is due to heightened inflammatory cytokine release from mutant lesional macrophages. However, given CHIP is driven by several mutations, other haematopoietic lineages can be altered to promote CVD. In this review we explore the relationship between mutations in genes causing CHIP and atherothrombotic disorders, along with potential mechanisms of enhanced clonal outgrowth and potential therapies and strategies to slow CHIP progression.

Pubmed   Journal   ReadQx 

Growth Differentiation Factor-15: a Novel Biomarker for Predicting Risk of Venous Thromboembolism and Bleeding in Patients with Cancer.

No Abstract.

Pubmed   Journal   ReadQx 

HDL particle subclasses in statin treated patients with peripheral artery disease predict long-term survival.

Only the association between XL-HDL-P and CV-death sustained multivariable adjustment (1.49, 1.10-2.02), whereas associations for S-HDL-P and M-HDL-P were attenuated (0.76, 0.57-1.01; 0.80, 0.60-1.06). This study shows a novel association for a beneficial role of S-HDL-P and M-HDL-P but a negative association with higher cholesterol-rich XL-HDL-P for long-term outcome in well-treated patients with PAD. Thus, these results provide evidence that NMR-measured HDL particles identify patients at high CV residual risk beyond adequate lipid-lowering therapy.

Pubmed   Journal   ReadQx 

Identification of the novel G250R variant indicates a role for Thrombomodulin in modulating the risk for venous thromboembolism.

The different pattern of cell distribution suggested that the 250R variant is not able to sufficiently target the plasma membrane. Present findings add information to characterize protein structure-function relationships, further suggesting that misfolding of the protein modulates the expression of mature protein. Functional analyses of the 250R variant increase our understanding of the role of Thrombomodulin in coagulation and support the hypothesis that gene variants reducing protein functionality cause deficiency and behave as a thrombophilic risk factor.

Pubmed   Journal   ReadQx 

Interleukin 1 receptor 8 deficiency does not impact atherosclerosis.

No abstract.

Pubmed   Journal   ReadQx 


Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

Sarcopenia and cancer-related inflammation measurements in advanced gastric and junctional cancers - Ready for prime time?

Pubmed   Journal   ReadQx 

Blood

Blocking (iron) traffic in the gut.

Pubmed   Journal   ReadQx 

CNS prophylaxis in DLBCL: first do no harm.

Pubmed   Journal   ReadQx 

Firing up chromatin to forge T-ALL.

Pubmed   Journal   ReadQx 

GATA1: function through disorder.

Pubmed   Journal   ReadQx 

New immunotherapeutic target in myeloma.

Pubmed   Journal   ReadQx 

The rise of Apollo, protector of telomeres.

Pubmed   Journal   ReadQx 

Leukemia

The complex karyotype in hematological malignancies: a comprehensive overview by the Francophone Group of Hematological Cytogenetics (GFCH).

The evaluation of karyotype complexity is challenging, and it would be useful to have a consensus method for counting the number of chromosomal abnormalities (CAs). Although it is not possible to establish a single prognostic threshold for the number of CAs in al malignancies, a specific consensus prognostic cut-off must be defined for each individual disease. In order to standardize current cytogenetic practices and apply a single denomination, we suggest defining a low complex karyotype as having 3 CAs, an intermediate complex karyotype as having 4 CAs, and a highly complex karyotype as having 5 or more CAs.

Pubmed   Journal   ReadQx 


Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

Validation of single-gene noninvasive prenatal testing for sickle cell disease.

Pubmed   Journal   ReadQx 

Blood Cancer J

Epigenetic modifier gene mutations in chronic myeloid leukemia (CML) at diagnosis are associated with risk of relapse upon treatment discontinuation.

Pubmed   Journal   ReadQx 

Long-term trends in the loss in expectation of life after a diagnosis of chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2018.

Pubmed   Journal   ReadQx 

Nutrition perceptions, needs and practices among patients with plasma cell disorders.

Pubmed   Journal   ReadQx 

Subsequent anti-myeloma therapy after idecabtagene vicleucel treatment in patients with relapsed/refractory multiple myeloma: A single center analysis.

Pubmed   Journal   ReadQx 


Others

all remaining publications eg case reports, images of the month, etc…

Am J Hematol

13-month-old girl with hyporegenerative macrocytic anemia due to Brown-Vialetto-Van Laere syndrome 2.

Pubmed   Journal   ReadQx 

Breast implant-associated anaplastic large cell lymphoma.

Pubmed   Journal   ReadQx 

Pseudo-Pelger-Huët neutrophil morphology due to sodium valproate toxicity.

Pubmed   Journal   ReadQx 

Blood

De novo and relapsed immune thrombocytopenia after COVID-19 vaccines: results of French safety monitoring.

Pubmed   Journal   ReadQx 

Human Apollo deficiency causes IBMFS.

Pubmed   Journal   ReadQx 

Pure erythroid leukemia evolved from JAK2V617F-positive polycythemia vera: blast phase transformation along erythroid line.

Pubmed   Journal   ReadQx 

Blood Adv

Eshel A, Sharon I, Nagler A, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis. Blood Adv. 2022;6(2):568-573.

Pubmed   Journal   ReadQx 

Ferrari N, Ward G, Gewinner C, et al. Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma. Blood Adv. 2021;5(20):4003-4016.

Pubmed   Journal   ReadQx 

Fertility Testing Knowledge and Attitudes in Male Adolescents and Young Adults with SCD and Their Caregivers: A Pilot Study.

Pubmed   Journal   ReadQx 

Haploidentical donor-derived memory CAR-T cells: first in human experience and in vitro correlative study.

Pubmed   Journal   ReadQx 

Singh A, Brandow AM, Panepinto JA. COVID-19 in individuals with sickle cell disease/trait compared with other Black individuals. Blood Adv. 2021;5(7):1915-1921.

Pubmed   Journal   ReadQx 

Transplant Outcomes After CPX-351 vs 7+3 in Older Adults With Newly Diagnosed High-risk and/or Secondary AML.

Pubmed   Journal   ReadQx 

Leukemia

CD99 as a novel therapeutic target on leukemic progenitor cells in FLT3-ITDmut AML.

Pubmed   Journal   ReadQx